tbuckley/cabot-search huggingface dataset:
Clinical and Molecular Determinants of Clonal Evolution in Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria
Authors: Carmelo Gurnari, Simona Pagliuca, Pedro Henrique Prata, Jacques-Emmanuel Galimard, Luiz Fernando B. Catto, Lise Larcher, Marie Sebert, Vincent Allain, Bhumika J. Patel, Arda Durmaz, Andre L. Pinto, Mariana C.B. Inacio, Lucie Hernandez, Nathalie Dhedin, Sophie Caillat-Zucman, Emmanuelle Clappier, Flore Sicre de Fontbrune, Maria Teresa Voso, Valeria Visconte, Régis Peffault de Latour, Jean Soulier, Rodrigo T. Calado, Gérard Socié, Jaroslaw P. Maciejewski
Journal: Journal of Clinical Oncology (2022)

PURPOSE Secondary myeloid neoplasms (sMNs) remain the most serious long-term complications in patients with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). However, sMNs lack specific predictors, dedicated surveillance measures, and early therapeutic interventions. PATIENTS AND METHODS We studied a multicenter, retrospective cohort of 1,008 patients (median follow-up 8.6 years) with AA and PNH to assess clinical and molecular determinants of clonal evolution. RESULTS Although none of the patients transplanted upfront (n = 117) developed clonal complications (either sMN or secondary PNH), the 10-year cumulative incidence of sMN in nontransplanted cases was 11.6%. In severe AA, older age at presentation and lack of response to immunosuppressive therapy were independently associated with increased risk of sMN, whereas untreated patients had the highest risk among nonsevere cases. The elapsed time from AA to sMN was 4.5 years. sMN developed in 94 patients. The 5-year overall survival reached 40% and was independently associated with bone marrow blasts at sMN onset. Myelodysplastic syndrome with high-risk phenotypes, del7/7q, and ASXL1, SETBP1, RUNX1, and RAS pathway gene mutations were the most frequent characteristics. Cross-sectional studies of clonal dynamics from baseline to evolution revealed that PIGA/human leukocyte antigen lesions decreased over time, being replaced by clones with myeloid hits. PIGA and BCOR/L1 mutation carriers had a lower risk of sMN progression, whereas myeloid driver lesions marked the group with a higher risk. CONCLUSION The risk of sMN in AA is associated with disease severity, lack of response to treatment, and patients' age. sMNs display high-risk morphological, karyotypic, and molecular features. The landscape of acquired somatic mutations is complex and incompletely understood and should be considered with caution in medical management.
Cost-Effectiveness of Pharmacologic Treatment Options for Women With Endocrine-Refractory or Triple-Negative Metastatic Breast Cancer
Authors: Stephanie B. Wheeler, Jason Rotter, Anagha Gogate, Katherine E. Reeder-Hayes, Sarah W. Drier, Donatus U. Ekwueme, Temeika L. Fairley, Gabrielle B. Rocque, Justin G. Trogdon
Journal: Journal of Clinical Oncology (2022)

Treatments for endocrine-refractory or triple-negative metastatic breast cancer (mBC) are modestly effective at prolonging life and improving quality of life but can be extremely expensive. Given these tradeoffs in quality of life and cost, the optimal choice of treatment sequencing is unclear. Cost-effectiveness analysis can explicitly quantify such tradeoffs, enabling more informed decision making. Our objective was to estimate the societal cost-effectiveness of different therapeutic alternatives in the first- to third-line sequences of single-agent chemotherapy regimens among patients with endocrine-refractory or triple-negative mBC.
Correction: Obesity and risk of female reproductive conditions: A Mendelian randomisation study
Authors: Samvida S. Venkatesh, Teresa Ferreira, Stefania Benonisdottir, Nilufer Rahmioglu, Christian M. Becker, Ingrid Granne, Krina T. Zondervan, Michael V. Holmes, Cecilia M. Lindgren, Laura B. L. Wittemans
Journal: PLoS Medicine (2022)

[This corrects the article DOI: 10.1371/journal.pmed.1003679.].
XL-ing at Induction of Apoptosis in Kidney Cancer through Inhibition of BCL-XL
Authors: Naitao Wang, A. Ari Hakimi, Yu Chen
Journal: Clinical Cancer Research (2022)

Through analysis of the cancer dependency map of CRISPR and short hairpin RNA datasets, the antiapoptotic BCL-XL was found to be a selective dependency in kidney cancer. Among kidney cancers, BCL-XL inhibition is most active in those with a mesenchymal gene signature, which portends a poor prognosis and response to current therapies. See related article by Grubb et al., p. 4689
A Quantitative, Qualitative, and Critical Assessment of Surgical Waste
Authors: Myles E. Tieszen
Journal: JAMA (1992)

<h3>Objectives.</h3> —To quantitatively and qualitatively evaluate the surgical waste produced from several common surgical procedures, define categories of waste that might be readily separated for alternative disposal practices or substitution, and determine the change in surgical waste output that elimination or alternative handling methods may effect. <h3>Design.</h3> —A case series evaluating the surgical waste from five types of surgical procedures including operations of the back, heart, abdomen, hip and knee, and herniorrhaphies, prospectively identified and allocated at the availability of the investigator. <h3>Setting.</h3> —A single tertiary community teaching hospital. <h3>Outcome Measures.</h3> —Weight, volume, and percentage of disposable linen, paper, and plastic plus miscellaneous material from surgical waste with a later subset separating plastics from miscellaneous items to completely identify all categories. <h3>Results.</h3> —Surgical waste weighing 610.5 lb (274.7 kg) and occupying 171.6 cu ft (5.1 m<sup>3</sup>) from 27 cases was examined. Disposable linens accounted for 39% of the weight; paper, 7%; plastic, 26%; and miscellaneous waste, 27%. By volume, disposable linen and paper accounted for 69%; plastic, 23%; and miscellaneous waste, 7%. Disposable linen, paper, and recyclable plastic accounted for 73±7% (mean±SD) by weight and 93%±4% by volume of total surgical waste. <h3>Conclusion.</h3> —Nationally, annual surgical waste from these five procedures weighs 5.1×10<sup>7</sup>lb (2.3×10<sup>7</sup>kg) and occupies 1.4×10<sup>7</sup>cu ft (4.0×10<sup>5</sup>m<sup>3</sup>). By using reusable linen products and engaging in recycling methods currently available and feasible, we estimate that weight reductions of 73% and volume reductions of 93% in surgical waste are possible. (<i>JAMA</i>. 1992;267:2765-2768)
HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression
Authors: Tatsuo Kawai, A. Benedict Cosimi, Thomas R. Spitzer, Nina Tolkoff-Rubin, Manikkam Suthanthiran, Susan L. Saidman, Juanita Shaffer, Frederic I. Preffer, Ruchuang Ding, Vijay Sharma, Jay A. Fishman, Bimalangshu Dey, Dicken S.C. Ko, Martin Hertl, Nelson B. Goes, Waichi Wong, Winfred W. Williams, Robert B. Colvin, Megan Sykes, David H. Sachs
Journal: New England Journal of Medicine (2008)
Assessment of Caregivers’ Burden When Caring for Patients With Pancreatic and Periampullary Cancer
Authors: Zhi Ven Fong, Jonathan Teinor, Theresa P Yeo, Dee Rinaldi, Jonathan B Greer, Harish Lavu, Motaz Qadan, Fabian M Johnston, Cristina R Ferrone, David C Chang, Charles J Yeo, Christopher L Wolfgang, Andrew L Warshaw, Keith D Lillemoe, Carlos Fernandez-del Castillo, Matthew J Weiss, Jennifer L Wolff, Albert W Wu
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Family and other unpaid caregivers play an active role in the recovery of individuals with pancreatic and periampullary cancer after pancreatectomy. However, little is known about caregivers’ experiences and how to better support them. Methods Caregivers accompanying patients to 1-month postpancreatectomy visits at 3 hospitals completed an electronic survey between November 2018 and February 2020. We examine measures of absenteeism and work productivity loss among the subset of caregivers who reported working for pay and comparatively assess caregiver experiences by employment status. All analyses were performed as 2-sided tests. Results Of 265 caregivers approached for study participation, 240 (90.6%) enrolled. Caregivers were primarily female (70.8% female, 29.2% male) and spouses (58.3%) or adult children (25.8%) of patients, with a median age of 60 years. Of the 240 caregivers included in the study, 107 (44.6%) worked for pay. Nearly half (44.4%) of working caregivers reported being absent from work because of caregiving amounting to a 14% loss in work hours. While at work, 58.9% of working caregivers reported increased work difficulty as a result of caregiving. Taken together, an estimated 59.7% loss in work productivity was experienced because of caregiving in the month following pancreatectomy. After adjustment for sociodemographic factors, working (vs nonworking) caregivers reported increased financial (odds ratio [OR] = 2.32; P = .04) and emotional (OR = 1.93; P = .04) difficulties and daily activity restrictions (OR = 1.85; P = .048). Conclusions Working caregivers of patients with pancreatic and periampullary cancer experience negative impacts on work and productivity, and caregiving-related financial and emotional difficulties may be amplified. This study highlights the need for workplace policies to support unpaid cancer caregiving.
Preliminary Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food — Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2015–2018
Authors: Danielle M. Tack, Ellyn P. Marder, Patricia M. Griffin, Paul R. Cieslak, John Dunn, Sharon Hurd, Elaine Scallan, Sarah Lathrop, Alison Muse, Patricia Ryan, Kirk Smith, Melissa Tobin-D’Angelo, Duc J. Vugia, Kristin G. Holt, Beverly J. Wolpert, Robert Tauxe, Aimee L. Geissler
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Foodborne diseases represent a major health problem in the United States.The Foodborne Diseases Active Surveillance Network (FoodNet) of CDC's Emerging Infections Program monitors cases of laboratory-diagnosed infection caused by eight pathogens transmitted commonly through food in 10 U.S. sites.*This report summarizes preliminary 2018 data and changes since 2015.During 2018, FoodNet identified 25,606 infections, 5,893 hospitalizations, and 120 deaths.The incidence of most infections is increasing, including those caused by Campylobacter and Salmonella, which might be partially attributable to the increased use of culture-independent diagnostic tests (CIDTs).The incidence of Cyclospora infections increased markedly compared with 2015-2017, in part related to large outbreaks associated with produce (1).More targeted prevention measures are needed on produce farms, food animal farms, and in meat and poultry processing establishments to make food safer and decrease human illness.FoodNet conducts active, population-based surveillance for laboratory-diagnosed infections caused by Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin-producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia in 10 sites covering 15% of the U.S. population (approximately 49 million persons in 2017).FoodNet is a collaboration among CDC, 10 state health departments, the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS), and the Food and Drug Administration (FDA).Bacterial infections are defined as isolation of the bacterium from a clinical specimen or detection of pathogen antigen, nucleic acid sequences, or, for STEC, † Shiga toxin or Shiga toxin genes.Listeria cases are defined as isolation of L. monocytogenes or detection of its nucleic acid sequences from a normally sterile site or from placental or fetal tissue in cases of miscarriage or stillbirth.Cyclospora infections are defined as detection of the parasite from a clinical specimen by direct fluorescent antibody, polymerase chain reaction, or light microscopy.Hospitalizations occurring within 7 days of specimen collection * Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, Tennessee, and selected counties in California, Colorado, and New York (https://www.cdc.gov/foodnet).† STEC cases are defined as identification of Shiga toxin or its genes by any laboratory; it is not possible to distinguish among serogroups using CIDTs.
Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged ≥65 Years: Updated Recommendations of the Advisory Committee on Immunization Practices
Authors: Almea Matanock, Grace Lee, Ryan Gierke, Miwako Kobayashi, Andrew Leidner, Tamara Pilishvili
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Recommendations for use of vaccines in children, adolescents, and adults are developed by the Advisory Committee on Immunization Practices (ACIP).ACIP is chartered as a federal advisory committee to provide expert
2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative
Authors: Christian Dejaco, Yogesh P Singh, Pablo Perel, Andrew Hutchings, Dario Camellino, Sarah Mackie, Andy Abril, Artur Bachta, Peter Balint, Kevin Barraclough, Lina Bianconi, Frank Buttgereit, Steven Carsons, Daniel Ching, Maria Cid, Marco Cimmino, Andreas Diamantopoulos, William Docken, Christina Duftner, Billy Fashanu, Kate Gilbert, Pamela Hildreth, Jane Hollywood, David Jayne, Manuella Lima, Ajesh Maharaj, Christian Mallen, Victor Martinez-Taboada, Mehrdad Maz, Steven Merry, Jean Miller, Shunsuke Mori, Lorna Neill, Elisabeth Nordborg, Jennifer Nott, Hannah Padbury, Colin Pease, Carlo Salvarani, Michael Schirmer, Wolfgang Schmidt, Robert Spiera, David Tronnier, Alexandre Wagner, Madeline Whitlock, Eric L Matteson, Bhaskar Dasgupta
Journal: Annals of the Rheumatic Diseases (2015)

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.
Will EMTALA Be There for People with Pregnancy-Related Emergencies?
Authors: Sara Rosenbaum, Alexander Somodevilla, Maria Casoni
Journal: New England Journal of Medicine (2022)

Interview with Prof. Sara Rosenbaum on the conflict between EMTALA and restrictive state abortion laws. (15:46)Download A showdown has been set in motion between restrictive state abortion laws and EMTALA, which commands hospitals to make medically sound efforts to avert deterioration when a patient's health is in danger.
Phylogenomics Uncovers Evolutionary Trajectory of Nitrogen Fixation in Cyanobacteria
Authors: Meng-Yun Chen, Wen-Kai Teng, Liang Zhao, Bo-Ping Han, Li-Rong Song, Wen-Sheng Shu
Journal: Molecular Biology and Evolution (2022)

Abstract Biological nitrogen fixation (BNF) by cyanobacteria is of significant importance for the Earth’s biogeochemical nitrogen cycle but is restricted to a few genera that do not form monophyletic group. To explore the evolutionary trajectory of BNF and investigate the driving forces of its evolution, we analyze 650 cyanobacterial genomes and compile the database of diazotrophic cyanobacteria based on the presence of nitrogen fixation gene clusters (NFGCs). We report that 266 of 650 examined genomes are NFGC-carrying members, and these potentially diazotrophic cyanobacteria are unevenly distributed across the phylogeny of Cyanobacteria, that multiple independent losses shaped the scattered distribution. Among the diazotrophic cyanobacteria, two types of NFGC exist, with one being ancestral and abundant, which have descended from diazotrophic ancestors, and the other being anaerobe-like and sparse, possibly being acquired from anaerobic microbes through horizontal gene transfer. Interestingly, we illustrate that the origin of BNF in Cyanobacteria coincide with two major evolutionary events. One is the origin of multicellularity of cyanobacteria, and the other is concurrent genetic innovations with massive gene gains and expansions, implicating their key roles in triggering the evolutionary transition from nondiazotrophic to diazotrophic cyanobacteria. Additionally, we reveal that genes involved in accelerating respiratory electron transport (coxABC), anoxygenic photosynthetic electron transport (sqr), as well as anaerobic metabolisms (pfor, hemN, nrdG, adhE) are enriched in diazotrophic cyanobacteria, representing adaptive genetic signatures that underpin the diazotrophic lifestyle. Collectively, our study suggests that multicellularity, together with concurrent genetic adaptations contribute to the evolution of diazotrophic cyanobacteria.
Supporting, Not Reporting — Emergency Department Ethics in a Post- <i>Roe</i> Era
Authors: Katie Watson, Maureen Paul, Susan Yanow, Jay Baruch
Journal: New England Journal of Medicine (2022)

Interview with Prof. Sara Rosenbaum on the conflict between EMTALA and restrictive state abortion laws. (15:46)Download The criminalization of abortion may result in an influx of patients for EDs. Ethical and legal obligations related to confidentiality, privacy, and duty of care apply in cases of self-managed abortion.
Evolutionary Changes in the Chromatin Landscape Contribute to Reorganization of a Developmental Gene Network During Rapid Life History Evolution in Sea Urchins
Authors: Phillip L Davidson, Maria Byrne, Gregory A Wray
Journal: Molecular Biology and Evolution (2022)

Abstract Chromatin configuration is highly dynamic during embryonic development in animals, exerting an important point of control in transcriptional regulation. Yet there exists remarkably little information about the role of evolutionary changes in chromatin configuration to the evolution of gene expression and organismal traits. Genome-wide assays of chromatin configuration, coupled with whole-genome alignments, can help address this gap in knowledge in several ways. In this study we present a comparative analysis of regulatory element sequences and accessibility throughout embryogenesis in three sea urchin species with divergent life histories: a lecithotroph Heliocidaris erythrogramma, a closely related planktotroph H. tuberculata, and a distantly related planktotroph Lytechinus variegatus. We identified distinct epigenetic and mutational signatures of evolutionary modifications to the function of putative cis-regulatory elements in H. erythrogramma that have accumulated nonuniformly throughout the genome, suggesting selection, rather than drift, underlies many modifications associated with the derived life history. Specifically, regulatory elements composing the sea urchin developmental gene regulatory network are enriched for signatures of positive selection and accessibility changes which may function to alter binding affinity and access of developmental transcription factors to these sites. Furthermore, regulatory element changes often correlate with divergent expression patterns of genes involved in cell type specification, morphogenesis, and development of other derived traits, suggesting these evolutionary modifications have been consequential for phenotypic evolution in H. erythrogramma. Collectively, our results demonstrate that selective pressures imposed by changes in developmental life history rapidly reshape the cis-regulatory landscape of core developmental genes to generate novel traits and embryonic programs.
Loss of hepatic SMLR1 causes hepatosteatosis and protects against atherosclerosis due to decreased hepatic VLDL secretion
Authors: Willemien van Zwol, Antoine Rimbert, Justina C. Wolters, Marieke Smit, Vincent W. Bloks, Niels J. Kloosterhuis, Nicolette C. A. Huijkman, Mirjam H. Koster, Umesh Tharehalli, Simon M. de Neck, Colin Bournez, Marceline M. Fuh, Jeroen Kuipers, Sujith Rajan, Alain de Bruin, Henry N. Ginsberg, Gerard J. P. van Westen, M. Mahmood Hussain, Ludger Scheja, Joerg Heeren, Philip Zimmerman, Bart van de Sluis, Jan Albert Kuivenhoven
Journal: Hepatology (2022)

The assembly and secretion of VLDL from the liver, a pathway that affects hepatic and plasma lipids, remains incompletely understood. We set out to identify players in the VLDL biogenesis pathway by identifying genes that are co-expressed with the MTTP gene that encodes for microsomal triglyceride transfer protein, key to the lipidation of apolipoprotein B, the core protein of VLDL. Using human and murine transcriptomic data sets, we identified small leucine-rich protein 1 ( SMLR1 ), encoding for small leucine-rich protein 1, a protein of unknown function that is exclusively expressed in liver and small intestine.
Treatment of Chronic Obstructive Pulmonary Disease With Orally Administered Theophylline
Authors: Michael R. Alexander
Journal: JAMA (1980)

Theophylline is commonly prescribed for chronic obstructive pulmonary disease (COPD), although controlled studies do not exist to support this use. We administered theophylline and placebo orally to 40 ambulatory COPD patients in a double-blind, crossover manner. Pulmonary function tests were conducted before and after isoproterenol nebulization on the final day of each four-week study period. Theophylline therapy produced small, but significant, increases over placebo in mean values. However, only the forced expiratory volume in 1 s was "improved," according to published criteria. There were no significant differences in subjective effects between treatment periods. Six patients were identified as "responders"; responder status could be predicted on the basis of improvement in flow rates after isoproterenol nebulization. Theophylline therapy is not beneficial to most COPD patients, and potential responders should be given carefully monitored therapeutic trials rather than arbitrarily being given maintenance therapy. (<i>JAMA</i>244:2286-2290, 1980)